This Mentored Research Scientist Development Award (K01) will investigate cellular and/or molecular mechanisms that may be responsible for an association between binge eating (a hallmark of obesity) and drug abuse and provide the candidate (Dr. Kimberlei Richardson) with novel training in the establishment of behavioral models, neuroendocrinology, and drug self-administration. Dr. Richardson's immediate objectives include successfully exploiting neurochemical, pharmacological, and behavioral strategies to demonstrate that the orexin system regulates the co-occurrence of binge-eating and drug addiction. This goal will be accomplished by developing an expertise in manipulating binge prone behavior models, establishing a relationship between the orexin system and binge prone behavior, becoming proficient in the use of radioimmunoassay to measure hormone levels, learning cannulae implantation, and learning drug self administration. In addition to the scientific aims of the studies presented, the ultimate goal of the proposal is to train the investigator with advanced behavioral and neuropharmacological techniques that, along with established expertise in tracing techniques and immunohistochemistry, will form the basis for a career as an independent investigator. The Career Development Plan involves mentorship in these behavioral and neuropharmacological techniques from Drs. Peter Kalivas (co-mentor), Robert Taylor(co-mentor) and Cheryl Sisk (collaborator). This plan utilizes the resources of three of the finest research institutions, Howard University, Medical University of South Carolina and Michigan State University. The experimental procedures will investigate the hypothesized role of the orexin system in the co-occurrence of binge eating and drug addiction. Recent literature has suggested that binge eating and drug abuse should be collectively characterized as "addictive behaviors" and have many overlapping features. The changes in neural reward processing as a result of binge eating may underlie behavioral and neurochemical tendencies toward drug addiction. The involvement of the orexin system in this reward processing is not known, but will be determined by the studies in this K01 application. The unique training outlined in the K01 will allow me to develop novel concepts to increase our understanding of the pharmacological influence of the orexins on the co-occurrence of binge eating and drug addiction, thereby identifying a specific target for intervention strategies to treat binge eating disorders and drug addiction. PUBLIC HEALTH RELEVANCE: The proposal investigates a neural system that may be responsible for the co-occurrence of eating disorders and drug abuse and provide knowledge that can improve therapeutic treatments for drug addiction and binge eating (a hallmark of obesity). Both disorders represent significant mental health problems that affect millions of Americans each year.